The long term goal of this project is to understand how variations in an organism's experience with its acoustic environment influence development and maintenance of neurons in the central nervous system. We have addressed this question by examining the postsynaptic influences of modifying the integrity or activity of afferent neurons in the developing brainstem auditory system of neonatal chicks and gerbils. During the past 8 years we have defined many of the presynaptic signals and many postsynaptic events which are important for trophic regulation by afferent innervation. During the proposed funding period we will continue this line of investigation by defining cellular events underlying transneuronal cell death and cell survival and by investigating intracellular signalling pathways that are altered by chronic changes in afferent activity. In addition, we will attempt to use deprivation- induced changes in presynaptic activity and in postsynaptic metabolic properties throughout the central auditory pathways as a predictor of long term structural and functional changes. We believe the results of these studies will provide valuable information regarding the cellular events underlying normal and abnormal ontogeny of neurons in the central nervous system.